Directory:

Tags:

A 2017 research project found that only 6 out of 18 FDA-approved blood glucose monitoring (BGM) systems tested were accurate

Each day BGM systems are used by millions of people with diabetes to help them self-manage their condition, and avoid devastating and costly complications

Thousands of similar smart devices support the prevention and self management of other chronic lifetime conditions, whose prevalence levels are high

The increasing demand for healthcare, its escalating costs, and rapidly evolving technologies are driving the growth of such remote self-managed devices

The most valuable aspect of such devices is the data they produce

These data tend to be under valued and under utilized by healthcare providers

This has created an opportunity for giant technology companies to enter the healthcare market with a plethora of smart devices and start utilizing the data they collect to enhance patient outcomes and lower costs

A 2017 research project, which tested 18 FDA-approved digital blood glucose monitoring (BGM) systems, which are used daily by millions of people with diabetes to check the concentration of glucose in their blood, found that only 6 were accurate. The research, led by David Klonoffof the Diabetes Research Institute at San Mateo, California, was funded by Abbott Laboratories.

This Commentary describes both traditional and next-generation BGM systems, and Klonoff’s research. The Commentary suggests that BGM systems are just one part of a vast, global, rapidly growing market for consumer healthcare devices, and argues that the most valuable aspect of these devices is the data they collect. With some notable exceptions, healthcare professionals do not optimally utilize these data to enhance care and reduce costs. This has created for an opportunity for technology companies to enter the healthcare market and re-engineer primary care. The one thing, which might slow the march of giant technology companies into mainstream healthcare, is the privacy issue.

Traditional and next-generation BGM systems

Traditional BGM systems

Regularly, each day, BGM systems are used by millions of people with diabetes to help them manage their condition. Managing diabetes varies from individual to individual, and peoples with diabetes usually self-monitor their blood glucose concentration from a small drop of capillary blood taken from a finger prick. They then apply the blood to a chemically active disposable 'test-strip'. Different manufacturers use different technology, but most systems measure an electrical characteristic, and use this to determine the glucose level in the blood. Such monitoring is the most common way for a person with diabetes to understand how different foods, medications, and activities affect their condition. The challenge for individuals with diabetes is that blood glucose levels have to be tested up to 12 times a day. People obliged to do this find finger pricking painful, inconvenient and intrusive, and, as a consequence, many people with diabetes do not check their glucose levels as frequently as they should, and this can have significant health implications. If your levels drop too low, you face the threat of hypoglycemia, which can cause confusion or disorientation, and in its most severe forms, loss of consciousness, coma or even death. Conversely, if your blood glucose levels are too high over a long period, you risk heart disease, blindness, renal failure and lower limb amputation.

Next generation BGM systemAbbott Laboratories Inc. markets a BGM system, which eliminates the need for routine finger pricks that are necessary when using traditional glucose monitors. Instead of finger pricks and strips, the BGM system, which measures interstitial fluid glucose levels, comprises a small sensor and a reader. An optional companion app for Android mobile devices is also available. The sensor is a few centimetres in diameter and is designed to stay in place for 10 days. It is applied to the skin, usually on the upper arm. A thin (0.4 mm), flexible and sterile fibre within the sensor is inserted in the skin to a depth of 5 mm. The fibre draws interstitial fluid from the muscle into the sensor, where glucose levels are automatically measured every minute and stored at 15-minute intervals for 8 hours. Glucose levels can be seen at any time by scanning the reader over the sensor. When scanned the sensor provides an answer immediately. It also shows an 8-hour history of your blood glucose levels, and a trend arrow showing the direction your glucose is heading. The device avoids the pain, and inconvenience caused by finger-prick sampling, which can deter people with diabetes from taking regular measurements. In the UK the system costs £58 for the reader, plus £58 for a disposable sensor, which must be replaced every 10 days and from November 2017 have been available on the NHS. Abbott Laboratories is a global NASDAQ traded US MedTech Company, with a market cap of US$86bn; annual revenues of US$21bn, and a diabetes care division, which produces annual revenues of some US$600m.

Klonoff’s research on BGM systems

BGM systems used by Klonoff and his team for their research were acquired over-the-counter and independent of their manufacturers. All were tested according to a protocol developed by a panel of experts in BGM surveillance testing.

Klonoff’s research specified that for a BGM system to be compliant, a blood glucose value must be within 15% of a reference plasma value for a blood glucose >100 mg/dl, and within 15 mg/dl of a reference plasma value for a blood glucose approved” a BGM system had to pass all 3 trials. Only 6 out of 18 passed by achieving an overall compliance rate of 95% or higher.

The FDA

Klonoff’s findings add credibility to patients’ concerns about the accuracy of BGM systems, which triggered responses from both manufactures and the US Food and Drug Administration (FDA). Manufacturers suggest that increasing the accuracy of BGM systems would raise their costs, and reduce their availability, which patients do not want. The FDA tightened approvals for BGM systems, and in 2016 issued 2 sets of guidelines, one for clinical settings, and another for personal home-use. The guidelines only apply to new products, and do not impact BGM systems already on the market. So while the FDA’s tighter accuracy requirements are a positive change, there are a significant number of less-accurate BGM systems still on the market.

Next generation BGM systems use ‘sensing’ technology, and have the capacity to automatically track and send blood glucose readings to the user’s smartphone, then onto their healthcare provider through the cloud where they can be amalgamated with other data. Analytics can then track an individual’s data, and compare them to larger aggregated data sets to detect trends, and provide personalized care.

Large rapidly growing remote self-managed device market

Although BGM systems address a vast global market, they represent just one part of a much larger, rapidly growing, remote monitoring market to help prevent and self-manage all chronic lifetime conditions, while improving healthcare utilization, and reducing costs. In 2015 some 165,000 healthcare apps were downloaded more than 3bn times. Of these, 44% were medical apps, and 12% were apps for managing chronic lifetime conditions. Today, mobile devices enable people to use their smartphones to inspect their eardrums, detect sleep apnoea, test haemoglobin, vital signs such as blood pressure, and oxygen concentration in the blood. This is a significant advance from the early precursor of activity tracker and step counting.

Chronic lifetime conditions21st century healthcare in developed countries is predominantly about managing chronic lifetime illnesses such as diabetes, cancer, heart disease and respiratory conditions. These 4 diseases have high prevalence levels, relatively poor outcomes, and account for the overwhelming proportion of healthcare costs. For instance, in the US alone, almost 50% of adults (117m) suffer from a chronic lifetime condition, and 25% have multiple chronic conditions. 86% of America’s $2.7 trillion annual health care expenditures are for people with chronic health conditions. This chronic disease pattern is replicated throughout the developed world, and has significant healthcare utilization and cost implications for public and private payers, individuals, and families.

Healthcare providers tend not to optimally utilize data

Although personal remote devices are increasingly important in the management of chronic conditions, the data these devices create are underutilized, despite their potential for improving outcomes and reducing costs. This is partly because doctors and health providers neither have the capacity nor the resources to exploit the full potential of these data; partly because doctors tend to resist technology to improve doctor-patient interactions, and partly because remote healthcare devices have not been validated for clinical use.

ValidationAlthough health professionals tend to prefer to use more expensive medical grade devices, which ensure data validity, but often drive up costs, research validating the data collected by remote self-managed devices for clinical use is beginning to emerge. In 2016 Analog Devices, a US multinational semiconductor company specializing in data conversion and signal processing technology, and LifeQ, a private US company with advanced bio-mathematical capabilities, announced a joint venture to establish whether data from wearable’s are accurate enough for clinical use.

A study published in 2017 in the journal Nature Biotechnology, provides some validation for data derived from apps to be used clinically. Using ResearchKit, an open source framework introduced by Apple in 2015 that allows researchers and developers to create powerful apps for medical research, the 6-month study enrolled 7,600 smartphone users who completed surveys on how they used an app to manage their asthma. Researchers then compared these patient-reported data with similar data from traditional asthma research, and found that there were no significant differences. Although there still remains some methodological challenges, the findings gave scientists confidence that data derived from an app could be reliable enough for clinical research. If data from self-managed remote monitoring devices are validated, then such devices could be used to unobtrusively and cost effectively enter the daily lives of patients to collect meaningful healthcare patient data, which could be used to enhance outcomes. Early research adopters of ResearchKit include the University of Oxford, Stanford Medicine, and the Dana-Farber Cancer Institute.

Giant technology companies entering healthcare market

The increasing validation of data generated by mobile devices and the continued underutilization of such data by health providers has created an opportunity for giant global technology companies to enter the healthcare market by: (i) developing and marketing self-monitoring devices directly to consumers, (ii) collecting, integrating, storing and analysing data generated by these remote devices, and (iii) supporting research initiatives to validate data from remote devices for clinical use.

Apple Inc.Just one example of giant technology companies entering the healthcare market is Apple Inc., which has a market cap of about US$1tn and 700m users worldwide. In 2017, Apple announced that it has been testing a BGM system, which pairs with the company’s existing Watch wearable. In August 2017, the US Patent and Trademark Office officially published a series of 50 newly granted patents to Apple. One covers an invention relating to health data, and more specifically to a smartphone that computes health data.

The technology involves emitting light onto a user’s body part and measuring the amount of light reflected back. This data can then help to determine body fat, breathing and even emotional health. This, and other patents issued to Apple fuel rumors that the company is preparing to turn its flagship smartphone into a predominantly healthcare-focused device.

Takeaway

Given the size and momentum of technology giants entering the healthcare market, and given the powerful demographic, technological, social and economic drivers of this market, it seems reasonable to assume that in the medium term, giant technology companies are well positioned to dis-intermediate primary care doctors, and re-engineer primary care. One thing that could slow this march, is the question of privacy. Health records are as private as private gets - from alcohol or drug abuse to sexually transmitted diseases or details of abortions: things we may never want to reveal to employers, friends or even family members. Significantly, these data are permanent, and privacy at this point is non-negotiable.

Findings of an international clinical study published in The Lancet in 2017 suggest that 3.0mg of the drug liraglutide, may reduce diabetes risk by 80% in individuals with pre-diabetes and obesity, and thereby significantly contribute to the prevention of type-2 diabetes (T2DM). The study investigated whether 3.0mg of liraglutide would delay the onset of T2DM safely in people with pre-diabetes.

Liraglutide is the active solution in a drug marketed as Victoza, which obtained FDA approval in 2010. Victoza is available in 6 mg/ml pre‑filled pens, and is used as an adjunct to diet and exercise to improve glycaemic control in adults with T2DM. Victoza is used also as an add-on to other diabetes medicines, when these, together with exercise and diet, are not providing adequate control of blood glucose.

Pre-diabetes

Pre-diabetes is a condition that develops when your blood sugar levels are at the very high end of the normal range, but not quite high enough for a diagnosis of T2DM. Risk factors include age, weight and ethnicity. People of South Asian origin are up to six times more likely to develop pre-diabetes as a genetic susceptibility means they start to develop insulin resistance at a much lower Body Mass Index (BMI).With pre-diabetes your body begins to have trouble using the hormone insulin, which is necessary to transport glucose, which your body uses for energy, into your cells via the bloodstream. Pre-diabetes means that your body either does not make enough insulin or it does not use it well (insulin resistance).If you do not have enough insulin or if you are insulin resistant, you can build up too much glucose in your blood, leading to higher-than-normal blood glucose level and perhaps pre-diabetes. Blood glucose is measured using a test called HbA1c, which provides a picture of your blood sugar levels over the past two to three months. It counts the number of glucose molecules stuck to the red blood cells, which reveals how much sugar you have carried in your blood over the two to three month lifespan of the red blood cell. If your blood sugar is between 5.7 to 6.4%, this is called pre-diabetes (6.5 is officially diabetes). Dr Roni Sharvanu Saha, a consultant in acute medicine, diabetes and endocrinology at St George's Hospital, London describes pre-diabetes:

Prevalence and cost

It is estimated that 35% of adults in the UK, and 50% in the US now have pre-diabetes. Around 5-10% of these will progress to "full-blown" T2DM in any given year. Because there are no obvious symptoms for pre-diabetes the overwhelming majority of people with the condition do not know they have it, and are not aware of the long-term risks to their health, which include T2DM and its complications: heart attack, stroke, kidney failure, blindness and lower limb amputation. Over the past decade, the prevalence of T2DM has increased by almost two-thirds, and is now one of the world’s most common long-term health conditions.

An estimated £14bn is spent each year on treating diabetes and its complications in the UK. Treating obesity-linked illnesses costs £10bn a year. The annual medical cost of treating diabetes in the US is about US$176bn, and the cost of diabetes in reduced productivity is some US$69bn each year.

The gut-brain axis

The study published in The Lancet was led by John Wilding, Professor of Medicine, University of Liverpool, and is a continuation of work he started in 1996 when part of a team at Hammersmith Hospital in London, which first showed that the hormone GLP-1, on which liraglutide is based, was involved in the control of food intake.

Over the past two decades scientists have increased their understanding of the two-way communications between the gut and the brain, not only through nerve connections between the organs, but also through biochemical signals, such as hormones that circulate in the body. Dr Sufyan Hussain, Specialist Registrar and Honorary Clinical Lecturer in Diabetes, Endocrinology and Metabolism at Imperial College London, describes the gut-brain axis.

Targeting gut-brain pathways

An increasing number of different gut microbial species are now postulated to regulate brain function in health and disease. The westernized diet, which is high in saturated fats, red meats, and carbohydrates, and low in fresh fruits and vegetables, whole grains, seafood, and poultry, is hypothesized to be the cause of high obesity levels in many countries. For example, 63% and 69% of adults in the UK and US respectively are either overweight or obese, and therefore at risk of T2DM. Experimental and epidemiological evidence suggest that the gut microbiota is responsible for significant immunologic, neuronal, and endocrine changes that lead to obesity. The gut–brain axis influences obesity, and researchers such as Wilding have targeted communication pathways between the nervous system and the digestive system in an attempt to treat metabolic disorders.

Bariatric surgery and diabetes

A previousHealthPad Commentary describes how bariatric surgery is associated with gut-brain signals, which promote the remission of diabetes in patients. Many of the mechanisms that underlie how bariatric surgery produces metabolic benefits remain unclear, but researchers do know that such surgical procedures elevate levels of the hormones peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) that help to reduce appetite and have effects on the central nervous system.

Liraglutide

Liraglutide is a GLP-1 receptor agonist, which interacts with the part of the brain that controls appetite and energy intake. The drug slows food leaving the stomach, helps prevent your liver from making too much sugar, and helps the pancreas to produce more insulin when your blood sugar levels are high. The most common side effects with liraglutide are nausea and diarrhoea.

The clinical study

The three-year study followed 2,254 adults with pre-diabetes at 191 research sites in 27 countries worldwide. Participants were randomly allocated to either liraglutide or a placebo delivered by injection under the skin once daily for 160 weeks. Participants in the study were also placed on a reduced calorie diet and advised to increase their physical activity. The study showed that three years of continuous treatment with once-daily 3.0mg of liraglutide, in combination with diet and increased physical activity, reduces the risk of developing T2DM by 80% and results in greater sustained weight loss compared to the placebo.

"On the basis of our findings, liraglutide 3.0mg can provide us with a new therapeutic approach for patients with obesity and pre-diabetes to substantially reduce their risk of developing type 2 diabetes and its related complications . . . . It is very exciting to see a laboratory observation translated into a medicine that has the potential to help so many people, even though it has taken over 20 years,” says Wilding.

World’s first nationwide diabetes prevention program

NHS England, Public Health England and Diabetes UK launched the world’s first nationwide diabetes prevention strategy, Healthier You, in 2016. It provides personal coaches to educate people at risk of T2DM in healthy eating and lifestyle, and personal trainers to provide bespoke physical exercise programs that are expected to help people lose weight. By 2020 Healthier You expects to be rolled out to the whole country with 100,000 referrals available each year after that.

Extrapolating from previous studies

International clinical studies have shown evidence that lifestyle interventions such as those used in Healthier You can prevent or delay the onset of T2DM. However, the validity of generalizing the results of previous prevention studies is uncertain. Interventions that work in some societies may not work in others, because social, economic, and cultural forces influence diet and exercise. The UK’s Public Accounts Committee has expressed doubts about the way Healthier You is setting about its task, and has warned that, "By itself, it will not be enough to stem the rising number of people with diabetes".

Failure of the diabetes establishment and the Public Accounts Committee

Healthier You is a slow, labor-intensive and expensive program, which is unlikely to have more than a relatively small impact.Let us explain. Assume that after 2020 Healthier You obtains its projected annual 100,000 referrals, and that they all successfully reduce their blood glucose levels with diet and exercise. Also assume that the prevalence of pre-diabetes in the UK does not increase, (which is not the case) then Healthier You will take more than 110 years to counsel the estimated 11.5m people in the UK with pre-diabetes: which is long after most people with pre-diabetes would have died from natural causes.

21st century communications

Successfully changing the diets and lifestyles of the 11.5m people in the UK believed to have pre-diabetes, and slowing their progression to T2DM will require 21st century technologies. Inexpensive and ubiquitous healthcare technologies used to educate and support diets and lifestyles abound. Increasingly people are demanding devices that track weight, blood pressure, daily exercise and diet. From apps to wearable’s, healthcare technology lets people feel in control of their health, while also providing health professionals with more patient data than ever before. With more than 100,000 healthcare apps, rapid growth in wearables, and 75% of the UK population now owning a smartphone, digital technology is well positioned to significantly improve healthcare education and management.

Takeaways

Has Healthier You missed the elephant in the room? Wilding’s study suggests that an exercise and diet program needs to be complemented with a sustained program of appropriate drugs if we are to reduce those with pre-diabetes from progressing to full blown T2DM. Further, simple arithmetic suggests that the education element of such a strategy about diet and lifestyle should leverage ubiquitous 21st century communications infrastructures if they are to be efficacious.